3-191329975-AGTAG-A

Position:

• chr3-191329975-AGTAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178335.3(CCDC50):​c.49+255_49+258del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 144,054 control chromosomes in the GnomAD database, including 4,770 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4770 hom., cov: 21)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

Genes affected

CCDC50 (HGNC:18111): (coiled-coil domain containing 50) This gene encodes a soluble, cytoplasmic, tyrosine-phosphorylated protein with multiple ubiquitin-interacting domains. Mutations in this gene cause nonsyndromic, postlingual, progressive sensorineural DFNA44 hearing loss. In mouse, the protein is expressed in the inner ear during development and postnatal maturation and associates with microtubule-based structures. This protein may also function as a negative regulator of NF-kB signaling and as an effector of epidermal growth factor (EGF)-mediated cell signaling. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

UTS2B (HGNC:30894): (urotensin 2B) Predicted to enable G protein-coupled receptor binding activity. Predicted to be involved in regulation of blood pressure. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-191329975-AGTAG-A is Benign according to our data. Variant chr3-191329975-AGTAG-A is described in ClinVar as [Benign]. Clinvar id is 1230089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.49+255_49+258del		intron_variant		ENST00000392455.9	NP_848018.1
UTS2B	NM_198152.5	c.-665+435_-665+438del		intron_variant		ENST00000340524.10	NP_937795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTS2B	ENST00000340524.10	c.-665+435_-665+438del		intron_variant		2	NM_198152.5	ENSP00000340526	P1
CCDC50	ENST00000392455.9	c.49+255_49+258del		intron_variant		1	NM_178335.3	ENSP00000376249	P3
CCDC50	ENST00000392456.4	c.49+255_49+258del		intron_variant		1		ENSP00000376250	A1
UTS2B	ENST00000432514.5	c.-832+435_-832+438del		intron_variant		5		ENSP00000401028

Frequencies

GnomAD3 genomes AF: 0.226 AC: 32548 AN: 143950 Hom.: 4764 Cov.: 21

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 32574 AN: 144054 Hom.: 4770 Cov.: 21 AF XY: 0.233 AC XY: 16187 AN XY: 69478

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.221

Alfa AF: 0.217 Hom.: 443

Bravo AF: 0.239

Asia WGS AF: 0.497 AC: 1653 AN: 3340

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10580681; hg19: chr3-191047764;